quetiapine-fumarate and Hypercholesterolemia

Second-generation antipsychotics (SGAs) are extensively prescribed for psychiatric disorders. Based on clinical observations, schizophrenia (SCZ) and affective disorder (AD) patients can experience different SGA side effects. The expanded use of SGAs in psychiatry suggests a need to investigate whether there is a difference in the incidence and severity of side effects related to diagnosis.. A comprehensive literature search was conducted to identify studies reporting side effects of four common prescribed SGAs (aripiprazole, quetiapine, risperidone and ziprasidone) in the treatment of SCZ or AD. Randomized controlled trials were included in this study if they administered oral SGAs as a monotherapy, in adult patients. The metabolic and extrapyramidal side effects were collected separately for each group, and then were combined in a meta-analysis.. 80 studies were included in the analysis (N = 14,319). Quetiapine treatment induced significantly higher low-density lipoprotein (LDL) and total blood cholesterol mean change in the SCZ group, relative to the AD group. Based on the results, the incidence of extrapyramidal side effects was more frequent in the AD group. Aripiprazole treatment led to significantly more akathisia incidence in the AD group, compared with the SCZ group.. The results suggest that SCZ patients may be more vulnerable to some SGA-induced metabolic disturbances, in which lifestyle risk factors and possible inherent genetic vulnerabilities may play a role. Most of the studied SGAs caused more movement disorders in AD patients than SCZ. It might be that an antipsychotic induces severity of side effect according to the phenotype.

Topics: Adult; Affective Disorders, Psychotic; Akathisia, Drug-Induced; Antipsychotic Agents; Aripiprazole; Dibenzothiazepines; Humans; Hypercholesterolemia; Incidence; Pharmacovigilance; Piperazines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Thiazoles

The authors conducted a multisite randomized controlled trial examining the strategy of switching from olanzapine, quetiapine, or risperidone to aripiprazole to ameliorate metabolic risk factors for cardiovascular disease.. Patients with schizophrenia or schizoaffective disorder with a body mass index ≥ 27 and non-high-density lipoprotein (non-HDL) cholesterol ≥ 130 mg/dl who were on a stable treatment dosage of olanzapine, quetiapine, or risperidone were randomly assigned to switch to ari-piprazole (N=109) for 24 weeks or stay on their current medication (N=106). All participants were enrolled in a behaviorally oriented diet and exercise program. Clinical raters were blinded to treatment assignment. The primary and key secondary outcomes were change in non-HDL cholesterol and efficacy failure, respectively.. The prespecified primary analysis included 89 switchers and 98 stayers who had at least one postbaseline non-HDL cholesterol measurement. The least squares mean estimates of non-HDL cholesterol decreased more for the switch group than for the stay group (-20.2 mg/dl and -10.8 mg/dl, respectively). Switching was associated with larger weight reductions (least squares mean=2.9 kg) and a net reduction of serum triglycerides of 32.7 mg/dl. Twenty-two switchers (20.6%) and 18 stayers (17.0%) experienced protocol-defined efficacy failure. Forty-seven switchers (43.9%) and 26 stayers (24.5%) discontinued the assigned antipsychotic medication before 24 weeks.. Switching to aripiprazole led to improvement of non-HDL cholesterol levels and other metabolic parameters. Rates of efficacy failure were similar between groups, but switching to aripiprazole was associated with a higher rate of treatment discontinuation. In the context of close clinical monitoring, switching from an antipsychotic with high metabolic risk to one with lower risk to improve metabolic parameters is an effective strategy.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Body Mass Index; Body Weight; Cholesterol; Cholesterol, LDL; Combined Modality Therapy; Dibenzothiazepines; Diet, Reducing; Drug Substitution; Exercise; Humans; Hypercholesterolemia; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risk; Risperidone; Schizophrenia; Treatment Outcome; Triglycerides

Topics: Adult; Dibenzothiazepines; Drug Interactions; Drug Synergism; Drug Therapy, Combination; Humans; Hypercholesterolemia; Hypertriglyceridemia; Male; Quetiapine Fumarate; Severity of Illness Index; Time Factors; Valproic Acid

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dibenzothiazepines; Drug Substitution; Humans; Hypercholesterolemia; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia

A case of intrahepatic cholestasis secondary to treatment with quetiapine in combination with lamotrigine and zopiclone, resulting in severe hypercholesterolaemia without overt lactescence of the plasma, is presented. Abundant lipoprotein-X was seen on lipoprotein electrophoresis. The patient was diagnosed and treated for hyponatraemia which was likely factitious and caused by hypercholesterolaemia. Cholestasis and hypercholesterolaemia resolved over a period of several months after the discontinuation of quetiapine.

Topics: Adult; Antipsychotic Agents; Cholestasis, Intrahepatic; Dibenzothiazepines; Humans; Hypercholesterolemia; Hyponatremia; Lipoprotein-X; Male; Quetiapine Fumarate

The goal of this study was to select some genes that may serve as good candidates for future studies of the direct effects (not explained by obesity) of some antipsychotics on hyperlipidemia. A search for single-nucleotide polymorphisms (SNPs) that may be associated with these direct effects was conducted. From a published cross-sectional sample, 357 patients on antipsychotics were genotyped using a DNA microarray with 384 SNPs. A total of 165 patients were taking olanzapine, quetiapine or chlorpromazine which may directly cause hypertriglyceridemia or hypercholesterolemia. Another 192 patients taking other antipsychotics were controls. A two-stage statistical analysis that included loglinear and logistic models was developed to select SNPs blindly. In a third stage, physiological knowledge was used to select promising SNPs. Known physiological mechanisms were supported for 3 associations found in patients taking olanzapine, quetiapine or chlorpromazine [acetyl-coenzyme A carboxylase alpha SNP (rs4072032) in the hypertriglyceridemia model, and for the neuropeptide Y (rs1468271) and ACCbeta, (rs2241220) in the hypercholesterolemia model]. These genes may be promising candidates for studies of the direct effects of some antipsychotics on hyperlipidemia.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Chlorpromazine; Cross-Sectional Studies; Dibenzothiazepines; Female; Gene Frequency; Genetic Variation; Genotype; Humans; Hypercholesterolemia; Hyperlipidemias; Hypertriglyceridemia; Lipids; Male; Olanzapine; Oligonucleotide Array Sequence Analysis; Pharmacogenetics; Polymorphism, Single Nucleotide; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic